Endogenous interleukin-6, but not tumor necrosis factor alpha, contributes to the development of toll-like receptor 4/myeloid differentiation factor 88-mediated acute arthritis in mice.

OBJECTIVE: To generate a mouse model of reactive arthritis (ReA), an aseptic synovitis that develops in joints distant from the primary bacterial infection site, to examine roles for Toll-like receptors (TLRs) that recognize bacterial components involved in the development of this arthritis, and to identify the cytokine(s) relevant to this arthritis. METHODS: Mice were treated with cell wall extract from Escherichia coli (ECW) gram-negative bacterium by injection into the footpads. Seven days later, the mice were challenged with lipopolysaccharide (LPS), a TLR-4 ligand, which was injected into the knee joint cavity. To investigate the cytokine(s) involved in this arthritis, mice deficient in various arthritogenic cytokines, such as interleukin-6 (IL-6), IL-12, IL-18, interferon-gamma, and tumor necrosis factor alpha (TNFalpha), were sequentially treated with ECW and LPS. RESULTS: ECW-primed mice manifested acute severe arthritis after intraarticular challenge with ECW or LPS, while unprimed mice exhibited modest changes after these challenges. Mutant mice lacking functional TLR-4 or myeloid differentiation factor 88 (MyD88), an adaptor molecule of TLR-4 signaling, were resistant to this arthritis. Although both TNFalpha and IL-6 were equally expressed in the joint after LPS challenge, Il6(-/-) mice, but not Tnf(-/-) mice, were resistant to ECW/LPS-induced arthritis. CONCLUSION: Our present results clearly indicate the importance of priming with ECW and the requirement of TLR-4/MyD88-mediated IL-6, but not TNFalpha, for the development of ECW/LPS-induced arthritis. LPS-induced IL-6, in the absence of TNFalpha, mediates LPS-induced arthritis. These results suggest that IL-6 is a rational target for therapeutic regimens for inflammatory arthritis, including ReA and rheumatoid arthritis.

Usefulness of ultrasonography for early recurrent myositis ossificans.

Myositis ossificans is a benign heterotopic ossifying condition of soft tissues. The lesion may cause persistent functional impairment of adjacent joints. Surgical intervention is often needed to regain normal function, even though a high recurrence rate is reported. In the present case, we found that recurrent myositis ossificans could not be demonstrated by radiography during the early stage. However, ultrasonography proved to be an excellent tool for detecting early recurrence of myositis ossificans and for distinguishing the condition from extraosseous sarcomas.